Rotator cuff injury is a debilitating condition that surgical intervention often fails to resolve; failure rates range between 30 - 94%. Muscle from 13 patients (4 females, 9 males; 49 - 65 yrs) with rotator cuff injury was studied at a cellular and molecular level to test the notion that it shows signs of atrophy, with or without features related to denervation with the hope of highlighting possible explanations for surgical failures. Satellite cell response to activation via a nitric oxide donor drug called isosorbide dinitrate (ISDN) was also investigated with the idea that satellite cells could be activated during the conservative management phase to promote muscle growth and repair. Supraspinatus and deltoid muscle biopsies taken during arthroscopic rotator cuff repair were analyzed in pairs for histology and showed muscle atrophy in the affected supraspinatus muscle. There were more small diameter fibres (p<0.005) and a smaller mean fibre diameter (17.9 ± 0.3μm) in supraspinatus vs. control deltoid muscle (21.8 ± 0.3μm & p<0.003). Alpha-bungarotoxin staining of acetylcholine receptors and western blotting for their gamma and epsilon subunits showed tendencies (p=0.13) to a linear arrangement and increased gamma to epsilon ratio respectively; both are signs of denervation. Response to ISDN showed more mitotically active Pax7+ satellite cells in supraspinatus muscle cultured with ISDN than in untreated supraspinatus or in the deltoid (p<0.03). Results are consistent with the notion that supraspinatus muscle of the injured rotator cuff is atrophic with possible denervation; together these features may increase susceptibility to muscle injury and surgical failure. Results also suggest the potential for the using ISDN to promote muscle growth and increase surgical success.